BackgroundTobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown. We explored the association between alcohol consumption and somatic copy-number alterations (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs, and compared with the effects of smoking on genetic alterations.MethodsSCNA and TP53 mutations in tumor samples were examined by high-resolution comparative genomic hybridization microarray 180K and by direct sequencing, respectively, and statistically analyzed for associations with alcohol consumption and smoking during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were considered statistically significant.ResultsA total of 248 patients with HNSCC were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption was significantly associated with SCNAs of oncogenes/oncosuppressors that were previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2) (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was associated with increased risk of TP53 mutations, but did not induce any significant SCNAs of oncogenes/oncosuppressors. ConclusionThese results suggest that both alcohol consumption and smoking had distinct effects on genetic alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce TP53 mutation, but may not trigger any SCNAs.
Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder forming hamartomas throughout the body. Facial angiofibromas (FAs) occur in 75% of TSC patients, which are often enlarged, impairing the appearance of the face, and reducing the patient's quality of life (QOL). The aim of this study was to characterize the impact of topical sirolimus treatment on the health-related QOL in patients with FA associated with TSC. Methods: We investigated a total of 33 patients who received sirolimus gel treatment for FA associated with TSC and assessed the changes in the health-related QOL using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey. SF-36 surveys were performed before and after 3 months of treatment. The conditions of the patients after using the sirolimus gel were categorized into the following three categories: "improved," "unchanged," and "aggravated." Adverse events were investigated using the CTCAE v5.0-JCOG. Results: The median age of the patients was 25 (range 14-55) years. After 3 months of sirolimus gel treatment, three scale scores of the SF-36, vitality (VT), social function (SF), and mental health (MH), were significantly improved compared to before the treatment. The VT and SF in patients who had improved FA were significantly better than those in the other patients. There were no significant differences in any scale scores between patients with and without adverse events at 3 months after the initiation of sirolimus gel treatment. Conclusions: This is the first report regarding improved health-related quality of life in patients treated with sirolimus gel for FA associated with TSC by using the SF-36. The three scale scores associated with mental health were significantly improved compared to before the treatment. The health-related QOL in patients receiving sirolimus gel treatment is more strongly affected by the treatment efficacy than adverse events. Mini-abstract: Sirolimus gel treatment improves the health-related QOL in patients with FA associated with TSC.
Background : Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder forming hamartomas throughout the body. Facial angiofibromas (FAs) occur in 75% of TSC patients, which are often enlarged, impairing the appearance of the face, and reducing the patient's quality of life (QOL). The aim of this study was to characterize the impact of topical sirolimus treatment on the health-related QOL in patients with FA associated with TSC. Methods : We investigated a total of 33 patients who received sirolimus gel treatment for FA associated with TSC and assessed the changes in the health-related QOL using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey. SF-36 surveys were performed before and after three months of treatment. The conditions of the patients after using the sirolimus gel were categorized into the following three categories: "improved," "unchanged," and "aggravated." Adverse events were investigated using the CTCAE v5.0-JCOG. Results : After 3 months of sirolimus gel treatment, three scale scores of the SF-36, vitality (VT), social function (SF), and mental health (MH), were significantly improved compared to before the treatment. The VT and SF in patients who had improved FA were significantly better than those in the other patients. There were no significant differences in any scale scores between patients with and without adverse events at three months after the initiation of sirolimus gel treatment. Conclusions : This is the first report regarding improved health-related quality of life in patients treated with sirolimus gel for FA associated with TSC by using the SF-36. The three scale scores associated with mental health were significantly improved compared to before the treatment. The health-related QOL in patients receiving sirolimus gel treatment is more strongly affected by the treatment efficacy than adverse events.
Introduction Owing to the complexity of their blood supply, renal tumors in horseshoe kidneys are sometimes technically challenging to resect through laparoscopic procedures. Case presentation A 75‐year‐old man presented with a 3‐cm lower‐pole mass in the right moiety of the horseshoe kidney. Indocyanine green administration allowed for the identification of the tumor's feeding artery, which was selectively clamped to perform laparoscopic partial nephrectomy. During the procedure, the patient was positioned in the modified supine position (30° semi‐lateral position), which enabled us to approach the branch of the left renal artery. Postoperative pathologic examination of the resected mass confirmed the diagnosis of pT1a clear cell renal cell carcinoma with negative surgical margins. Conclusion Our novel laparoscopic approach with indocyanine green fluorescence in the modified supine position facilitates the identification of and access to the tumor's feeding artery. This technique is advantageous for laparoscopic partial nephrectomy in patients with horseshoe kidney.
Background Docetaxel (DOC) has been widely accepted as a therapeutic option for castration‐resistant prostate cancer (CRPC). Evidence‐based clinical guidelines have stipulated its use up to 10 cycles in most health care systems. There has been a paucity of information regarding potential benefits of its use over 10 cycles. The purpose of this study is to re‐examine the rationale for the clinical guidelines concerning cycles of DOC in CRPC. Methods Between July 2007 and July 2016, a total of 122 CRPC patients received at least five cycles of DOC at Jikei University and its affiliate hospitals. Doses of DOC (75 mg/m 2) were administered every 3 to 4 weeks. Clinical outcomes between patients receiving extended cycles of DOC (≥11 cycles, extended [ex]‐DOC group) were compared to those receiving fewer (≤10 cycles, short‐DOC group). A subgroup of patients who had discontinued DOC owing to adverse events, but whose disease did not progress, were also considered for comparison (adverse events [AE] group). Overall survival from the induction of DOC was the primary outcome measure. Univariate and multivariate analyses were conducted to analyze variables associated with overall survival. Results The ex‐ and short‐DOC groups included 80 and 42 patients, respectively. Most baseline demographics did not differ between groups. However, in the short‐DOC group more patients had received abiraterone acetate and/or enzalutamide before chemotherapy, age at DOC induction was younger, and lactate dehydrogenase at DOC induction was higher. Overall survival was significantly longer in the ex‐DOC group compared to the short‐DOC group (median, 53 and 27 months, respectively; P = .04). A subgroup of 22 patients in AE group was compared to compensate for potential bias. Overall survival from the induction of DOC was comparable between AE group and ex‐DOC groups (median, 53 vs 53 months, respectively; P = 0.87). Univariate and multivariate analyses did not show any advantage of extended use of DOC on patient survival. Conclusions The results of this study failed to show the survival benefit of extended use of DOC over 10 cycles in CRPC patients in the era of innovative drugs such as abiraterone acetate, enzalutamide, and cabazitaxel. Further prospective studies are required to confirm our findings.
Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder forming hamartomas throughout the body. Facial angiofibromas (FAs) occur in 75% of TSC patients, which are often enlarged, impairing the appearance of the face, and reducing the patient's quality of life (QOL). The aim of this study was to characterize the impact of topical sirolimus treatment on the health-related QOL in patients with FA associated with TSC.Methods: We investigated a total of 33 patients who received sirolimus gel treatment for FA associated with TSC and assessed the changes in the health-related QOL using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey. SF-36 surveys were performed before and after three months of treatment. The conditions of the patients after using the sirolimus gel were categorized into the following three categories: "improved," "unchanged," and "aggravated." Adverse events were investigated using the CTCAE v5.0-JCOG.Results: The median age of the patients was 25 (range 14-55) years. After 3 months of sirolimus gel treatment, three scale scores of the SF-36, vitality (VT), social function (SF), and mental health (MH), were significantly improved compared to before the treatment. The VT and SF in patients who had improved FA were significantly better than those in the other patients. There were no significant differences in any scale scores between patients with and without adverse events at three months after the initiation of sirolimus gel treatment.Conclusions: This is the first report regarding improved health-related quality of life in patients treated with sirolimus gel for FA associated with TSC by using the SF-36. The three scale scores associated with mental health were significantly improved compared to before the treatment. The health-related QOL in patients receiving sirolimus gel treatment is more strongly affected by the treatment efficacy than adverse events. Mini-abstractSirolimus gel treatment improves the health-related QOL in patients with FA associated with TSC.
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